B anthracis-host interactionB炭疽杆菌宿主相互作用.pptVIP

Cytokine Subversion—and inducible transient organogenesis—by Bacillus anthracis Tom Kepler Center for Bioinformatics Computational Biology Duke University Medical Center Outline B. anthracis Cytokines TNF Spatial organization Inducible Transient Organogenesis Model and Results Mathematical Modeling and Category A pathogens Little/No Human data Naturally rare No experimentation Diversity among animal models Bacillus anthracis: lifecycle Endospore Dormant and highly resistant for decades Upon exposure to low pH, amino acids (e.g., macrophage phagosomes), germinates. Vegetative bacillus Grows within the host, eventually killing it. No host-host transmission Upon exposure to air, sporulates. B. anthracis: biochemistry Toxins Protective Antigen Heptameric binding to host cell surface receptors Mediates entry of EF and LF into host cell Edema Factor ATP → cAMP Inhibits neutrophil phagocytosis Lethal Factor Cleaves MAPKK Induces ROI, TNF, IL6 MAP Kinase Pathway Cytokines Communication molecules Proliferation Differentiation Regulation of Movement Pro-inflammatory TNF, IL1, IL6, … Anti-inflammatory IL10, IL4 Chemoattractant Viral subversion TNF Produced by monocytes/macrophages upon bacterial stimulation Low dose: chemoattraction, activation High dose: necrosis, apoptosis: Shock Soluble TNF receptor from cleavage of aggregated receptor Pathogen subversion of cytokines Viruses Bacteria Anti-inflammatory Inducible Transient Organogenesis Germinal center Synovial GC Granuloma Thymus Transplantation observations (M.L. Markert) Germinal Center-like structure in rheumatoid synovium Postdoctoral and Predoctoral Opportunities at [CB]2 Duke University Medical Center Center for Bioinformatics and Computational Biology New PhD program starting 2003 Postdoctoral Fellows Sought kepler@duke.edu 919 681 0620 * Lymph Node Germinal Center Mantle Light Zone Dark Zone T (paracortical) Zone macrophage intoxicated mf bacillus lethal toxin TNF B. anthracis - macrophage spatial interac